Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Outline of Final Research Achievements |
Here, we found that ELAS1, a twentynine amino acid peptide corresponding to the association domain of Cyclin G1 with protein phosphatase 2A, interacts with the B' gamma subunit of PP2A and competitively inhibits the association with Cyclin G1. We showed that ELAS1 induced apoptotic cell death in U2OS, a human osteosarcoma cells through prevention of dephosphorylation at Mdm2 pT218 and p53 pS46, following DNA double-strand break insults such as gamma-irradiation and irinotecan treatment. We also show that ELAS1 caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells, but not in normal KD cells. The adenovirus that express ELAS1 also killed SAS cells. Notably, Cy5 tagged ELAS1t, which contained only ten amino acids, also efficiently induced apoptosis in both DU145 and SAS cells, suggesting the usefulness of ELAS1t itself as a peptide. Taken together, our results suggest that ELAS1 is therapeutically useful as a peptide drug.
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